Susan B. Horwitz, PhD

2008-2009 BCRF Project:
Co-investigator: Hayley M. McDaid, PhD, Albert Einstein College of Medicine, New York, NY

Over the past year, Drs. Horwitz and McDaid have focused on generating Taxol–resistant cells, taking a unique approach that differs from prior strategies. They have exposed cells to Taxol in a manner that mimics the way patients are administered the drug. The data that is generated from analysis of these resistant lines will be more applicable to human breast tumors that have acquired resistance to Taxol. The researchers are studying the expression of DNA in Taxol-resistant breast cancer and have found genes that are inappropriately switched off and on in these cells, through what are called epigenetic mechanisms, utilizing novel methods developed at Albert Einstein College of Medicine.

They will expand on these studies by investigating another mechanism by which genes can be switched off and on in cells that are Taxol-resistant. This may be mediated by the action of microRNAs, which are small pieces of RNA that prevent functional proteins from being made in cells. As many as 30% of human genes are predicted to be regulated by miRNAs and Drs. Horwitz and McDaid will use specific technology to determine which microRNAs are involved in Taxol-resistance in breast cancer. Their results will lead to an in-depth understanding of Taxol-resistance that is necessary for strategies to overcome the problem of drug-resistance.

Bio:
Dr. Susan Band Horwitz is a Distinguished University Professor at the Albert Einstein College of Medicine and Associate Director for Therapeutics at the Albert Einstein Cancer Center. She grew up in Boston and after graduating from Bryn Mawr College, received her Ph.D in Biochemistry at Brandeis University.

Dr. Horwitz has had a continuing interest in natural products as a source of new drugs for the treatment of cancer. Her laboratory has made Taxol, a drug isolated from the yew plant, Taxus brevifolia, a major focus of its work. Although no one was interested in Taxol when she began her studies, today it is an important anti-tumor drug that has been given to over a million patients. Dr. Horwitz' research played an important role in encouraging the development of Taxol by the National Cancer Institute.

Dr. Horwitz and her collaborators demonstrated that the effects of Taxol were due to a novel interaction between the drug and microtubules, the latter being essential for the pairing and segregation of chromosomes during cell division. Her pioneering investigations and perceptive analysis of the results identified Taxol as a prototype of a new class of anti-tumor drugs. Extensive research has led to major insights into several aspects of the chemistry and biology of Taxol. Dr. Horwitz also has made significant contributions to our understanding of the molecular mechanisms underlying Taxol resistance in tumor cells.